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1.
Oncoimmunology ; 10(1): 1976439, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721946

RESUMO

Spatial information on the tumor immune microenvironment is of clinical relevance. Here, we aimed to quantify the spatial heterogeneity of lymphocytes and cancer cells and evaluated its prognostic value in patients with nasopharyngeal carcinoma (NPC). The scanned immunohistochemistry images of 336 NPC patients from two different hospitals were used to generate cell density maps for tumor and immune cells. Then, Getis-Ord hotspot analysis, a spatial statistic method used to describe species biodiversity in ecological habitats, was applied to identify cancer, immune, and immune-cancer hotspots. The results showed that cancer hotspots were not associated with any of the studied clinical outcomes, while immune-cancer hotspots predicted worse overall survival (OS) in the training cohort. In contrast, a high immune hotspot score was significantly associated with better OS (HR 0.41, 95% CI 0.22-0.77, P = .006), disease-free survival (DFS) (HR 0.43, 95% CI 0.24-0.75, P = .003) and distant metastasis-free survival (DMFS) (HR 0.40, 95% CI 0.20-0.81, P = .011) in NPC patients in the training cohort, and similar associations were also evident in the validation cohort. Importantly, multivariate analysis revealed that the immune hotspot score remained an independent prognostic indicator for OS, DFS, and DMFS in both cohorts. We explored the spatial heterogeneity of cancer cells and lymphocytes in the tumor microenvironment of NPC patients using digital pathology and ecological analysis methods and further constructed three spatial scores. Our study demonstrates that spatial variation may aid in the identification of the clinical prognosis of NPC patients, but further investigation is needed.

2.
Cancer Commun (Lond) ; 41(11): 1195-1227, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34699681

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

3.
Bot Stud ; 62(1): 13, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34568997

RESUMO

BACKGROUND: Agricultural management and temporal change including climate conditions and soil properties can result in the alteration of soil enzymatic activity and bacterial community, respectively. Therefore, different agricultural practices have been used globally to explore the soil quality. In this study, the temporal variations in soil property, enzymatic activity, and bacterial community at three successive trimester sampling intervals were performed in the soil samples of litchi orchards that were maintained under conventional and sustainable agricultural practices. RESULTS: Agricultural management found to significantly influence arylsulfatase, ß-glucosidase, and urease activities across time as observed by repeated-measures analysis of variance. Shannon and Simpson diversity indices, and the relative abundance of predominant Acidobacteria and Proteobacteria were significantly influenced by temporal change but not agricultural management. This suggested that soil enzymatic activity was more susceptible to the interaction of temporal change and agricultural management than that of the bacterial community. Multiple regression analysis identified total nitrogen, EC, and phosphorus as the significant predictors of acid phosphatase, arylsulfatase, and ß-glucosidase for explaining 29.5-39% of the variation. Moreover, the soil pH and EC were selected for the SOBS, Chao, ACE, and Shannon index to describe 33.8%, 79% of the variation, but no significant predictor was observed in the dominant bacterial phyla. Additionally, the temporal change involved in the soil properties had a greater effect on bacterial richness and diversity, and enzymatic activity than that of the dominant phyla of bacteria. CONCLUSIONS: A long-term sustainable agriculture in litchi orchards would also decrease soil pH and phosphorus, resulting in low ß-glucosidase and urease activity, bacterial richness, and diversity. Nevertheless, application of chemical fertilizer could facilitate the soil acidification and lead to adverse effects on soil quality. The relationship between bacterial structure and biologically-driven ecological processes can be explored by the cross-over analysis of enzymatic activity, soil properties and bacterial composition.

4.
Lancet ; 398(10297): 303-313, 2021 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-34111416

RESUMO

BACKGROUND: Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18-65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III-IVA, excluding T3-4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12-16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. FINDINGS: Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33-42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4-90·6]) than in the standard therapy group (75·7% [69·9-81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32-0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. INTERPRETATION: The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. FUNDING: The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Capecitabina/administração & dosagem , Quimioterapia Adjuvante/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Administração Metronômica , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
Bot Stud ; 62(1): 8, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34003387

RESUMO

BACKGROUND: The soil quality and health of the tea plantations are dependent on agriculture management practices, and long-term chemical fertilizer use is implicated in soil decline. Hence, several sustainable practices are used to improve and maintain the soil quality. Here, in this study, changes in soil properties, enzymatic activity, and dysbiosis in bacterial community composition were compared using three agricultural management practices, namely conventional (CA), sustainable (SA), and transformational agriculture (TA) in the tea plantation during 2016 and 2017 period. Soil samples at two-months intervals were collected and analyzed. RESULTS: The results of the enzyme activities revealed that acid phosphatase, arylsulfatase, ß-glucosidase, and urease activities differed considerably among the soils representing the three management practices. Combining the redundancy and multiple regression analysis, the change in the arylsulfatase activity was explained by soil pH as a significant predictor in the SA soils. The soil bacterial community was predominated by the phyla Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, and Bacteroidetes in the soil throughout the sampling period. Higher Alpha diversity scores indicated increased bacterial abundance and diversity in the SA soils. A significant relationship between bacterial richness indices (SOBS, Chao and ACE) and soil pH, K and, P was observed in the SA soils. The diversity indices namely Shannon and Simpson also showed variations, suggesting the shift in the diversity of less abundant and more common species. Furthermore, the agricultural management practices, soil pH fluctuation, and the extractable elements had a greater influence on bacterial structure than that of temporal change. CONCLUSIONS: Based on the cross-over analysis of the bacterial composition, enzymatic activity, and soil properties, the relationship between bacterial composition and biologically-driven ecological processes can be identified as indicators of sustainability for the tea plantation.

7.
Mol Cancer ; 20(1): 27, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541368

RESUMO

The development of immune checkpoint blockade (ICB)-based immunotherapy has dramatically changed methods of cancer treatment. This approach triggers a durable treatment response and prolongs patients' survival; however, not all patients can benefit. Accumulating evidence demonstrated that the efficacy of ICB is dependent on a robust antitumor immune response that is usually damaged in most tumors. Conventional chemotherapy and targeted therapy promote the antitumor immune response by increasing the immunogenicity of tumor cells, improving CD8+ T cell infiltration, or inhibiting immunosuppressive cells in the tumor microenvironment. Such immunomodulation provides a convincing rationale for the combination therapy of chemotherapeutics and ICBs, and both preclinical and clinical investigations have shown encouraging results. However, the optimal drug combinations, doses, timing, and sequence of administration, all of which affect the immunomodulatory effect of chemotherapeutics, as well as the benefit of combination therapy, are not yet determined. Future studies should focus on these issues and help to develop the optimal combination regimen for each cancer.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Terapia de Alvo Molecular , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/uso terapêutico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Tomada de Decisão Clínica , Gerenciamento Clínico , Suscetibilidade a Doenças , Sinergismo Farmacológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Imunomodulação/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia
8.
Mol Cancer ; 20(1): 14, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430876

RESUMO

Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.


Assuntos
Heterogeneidade Genética , Imunoterapia , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/terapia , Microambiente Tumoral , Estudos de Coortes , Genoma Humano , Humanos , Carcinoma Nasofaríngeo/genética , Prognóstico , Reprodutibilidade dos Testes , Microambiente Tumoral/genética
9.
J Clin Oncol ; 39(7): 840-859, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33405943

RESUMO

PURPOSE: The aim of this joint guideline is to provide evidence-based recommendations to practicing physicians and other healthcare providers on definitive-intent chemoradiotherapy for patients with stage II-IVA nasopharyngeal carcinoma (NPC). METHODS: The Chinese Society of Clinical Oncology (CSCO) and ASCO convened an expert panel of radiation oncology, medical oncology, surgery, and advocacy representatives. The literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2020. Outcomes of interest included survival, distant and locoregional disease control, and quality of life. Expert panel members used this evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 108 relevant studies to inform the evidence base for this guideline. Five overarching clinical questions were addressed, which included subquestions on radiotherapy (RT), chemotherapy sequence, and concurrent, induction, and adjuvant chemotherapy options. RECOMMENDATIONS: Evidence-based recommendations were developed to address aspects of care related to chemotherapy in combination with RT for the definitive-intent treatment of stage II to IVA NPC.Additional information is available at www.asco.org/head-neck-cancer-guidelines.


Assuntos
Quimiorradioterapia/normas , Oncologia/normas , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Consenso , Humanos , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Qualidade de Vida , Radioterapia (Especialidade)/normas , Resultado do Tratamento
10.
J Natl Cancer Inst ; 113(4): 471-480, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33094348

RESUMO

BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. METHODS: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. RESULTS: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. CONCLUSIONS: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.


Assuntos
Expressão Gênica , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Sensibilidade e Especificidade , Resultado do Tratamento
11.
Cancer Commun (Lond) ; 40(12): 721-737, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33038291

RESUMO

BACKGROUND: Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. METHODS: Bisulfite pyrosequencing was used to analyze zinc finger protein 582 (ZNF582) methylation in NPC tissues and cell lines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582-targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) and were confirmed by ChIP-qPCR and luciferase assay. RESULTS: ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo. ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and NRXN3. Both Nectin-3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. CONCLUSIONS: ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3, which may provide novel therapeutic targets for NPC treatment.


Assuntos
Metilação de DNA , Fatores de Transcrição Kruppel-Like/genética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nectinas/genética , Proteínas do Tecido Nervoso/genética , Linhagem Celular Tumoral , Epigênese Genética , Células HEK293 , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Regiões Promotoras Genéticas
12.
Front Oncol ; 10: 1469, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983982

RESUMO

We investigated the clinical characteristics, prognostic factors, and post-recurrence prognostic factors of early- and late-recurrence patients for nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiation therapy (IMRT). This was a single-center retrospective analysis of patients in China from January 2010 to December 2015. The prognostic factors for overall survival (OS) and post-recurrence OS of early- and late-recurrence patients were identified using univariate and multivariate Cox regression analyses. Of the 9,468 patients included, 409 (4.3%), 325 (3.4%), and 182(1.9%) developed purely local recurrence, purely regional recurrence, and locoregional recurrence during follow-up, respectively. In the purely local recurrence group, 192 patients (46.9%) developed early local recurrence (ETR), and 217 patients (53.1%) developed late local recurrence (LTR). Of the 192 ETR patients, multivariate Cox regression analysis revealed that age and gender were independent risk factors of OS, and post-recurrence best supportive treatment (PRBST) was associated with poorer post-recurrence OS. Of the 217 LTR patients, the results revealed that baseline value of EBV-DNA was an independent risk factor for OS, while PRBST was associated with poorer post-recurrence OS. In the purely regional recurrence group, 183 patients (56.3%) developed early regional recurrence (ENR), and 142 patients (43.7%) developed late regional recurrence (LNR). Of the 183 ENR patients, multivariate Cox regression analysis revealed that alcohol abuse and TNM stage were independent risk factors of OS, while alcohol drinkers and PRBST were associated with poorer post-recurrence OS. Of the 142 LNR patients, PRBST was associated with poorer post-recurrence OS. In the locoregional recurrence group, 87 patients (47.8%) developed early locoregional recurrence (ELR), and 95 patients (52.2%) developed late locoregional recurrence (LLR). Of the 87 ELR patients, multivariate Cox regression analysis revealed that N stage and TNM stage were independent risk factors of OS, and N2/3 stage and PRBST were associated with poorer post-recurrence OS. Of the 95 LLR patients, the results revealed that T stage was an independent risk factor for OS, while T3/4 stage and PRBST were associated with poorer post-recurrence OS. Patients with LTR/LNR/LLR demonstrate significantly better OS compared with patients with ETR/ENR/ELR, Nevertheless, post-recurrence OS between patients with ETR/ENR/ELR and LTR/LNR/LLR was not significantly different.

13.
Cell Res ; 30(11): 1024-1042, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32686767

RESUMO

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A+ dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A+ DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.


Assuntos
Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/imunologia , Análise de Célula Única , Transcriptoma/genética , Linfócitos B/imunologia , Comunicação Celular , Diferenciação Celular , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade , Células Matadoras Naturais/imunologia , Macrófagos/metabolismo , Monócitos/metabolismo , Células Mieloides/metabolismo , Carcinoma Nasofaríngeo/patologia , Fenótipo , Prognóstico , Processos Estocásticos , Análise de Sobrevida , Linfócitos T/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
14.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32690665

RESUMO

BACKGROUND: Tumor-infiltrating lymphocytes have been reported as prognostic markers in tumors. We aimed to assess the prognostic value of total T cell (CD3+) density, cytotoxic T cell (CD8+) density and memory T cell (CD45RO+) density in patients with nasopharyngeal carcinoma (NPC). METHODS: The expression of CD3, CD8 and CD45RO was detected by immunohistochemistry in the training (n=221) and validation cohorts (n=115). The densities of these three markers were quantified by digital pathology both in the tumor and stroma. Then, we developed the immune score based on the density of these three markers and further analyzed its prognostic value. RESULTS: The high density of CD3+, CD8+ and CD45RO+ T cells both in the tumor and/or stroma were significantly associated with the decrease in mortality in the training cohort, respectively. High immune score predicted a prolonged overall survival (OS) (HR 0.34, 95% CI 0.18 to 0.64, p=0.001, disease-free survival (DFS) (HR 0.44, 95% CI 0.25 to 0.78, p=0.005) and distant metastasis-free survival (DMFS) (HR 0.43, 95% CI 0.21 to 0.87, p=0.018) in NPC patients. The findings were confirmed in the validation cohort. Multivariate analysis revealed that immune score remained an independent prognostic indicator for OS, DFS and DMFS. In addition, we established a nomogram with the integration of all independent variables to predict individual risk of death. CONCLUSIONS: We established an immune score model, which provides a reliable estimate of the risk of death, disease progress and distant metastasis in NPC patients.


Assuntos
Linfócitos do Interstício Tumoral/imunologia , Carcinoma Nasofaríngeo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Prognóstico , Análise de Sobrevida
15.
Am Soc Clin Oncol Educ Book ; 40: 1-11, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32191137

RESUMO

Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) is endemic in Southern China, and the prognosis of this cancer has improved in part due to advances in radiotherapy (RT) techniques, broadened therapeutic options, and more precise prognostic stratification of patients. RT is the primary curative treatment of NPC, and the incorporation of chemotherapy (induction, concurrent, adjuvant) to RT has contributed to improved survival in patients with locoregionally advanced NPC. Concurrent chemoradiotherapy (CCRT) in combination with adjuvant or induction chemotherapy is now the standard treatment of locoregionally advanced NPC, but the ideal CCRT therapeutic strategy for NPC remains controversial. Plasma EBV DNA is the archetypal tumor-derived DNA in NPC, and three generations of studies have gradually expanded its clinical applications. Recently, the advent of whole exome/genome sequencing of NPC and the promising clinical activity of immune checkpoint inhibitors have also spurred interest in the development of newer biomarkers. This review will focus on two clinical advances in NPC research that have made substantial impact on the contemporary management of NPC: (1) The integration of plasma EBV DNA in an expanding spectrum of clinical indications, and the development of promising immune-related biomarkers; (2) the current development of CCRT with special emphasis on the use of induction and adjuvant chemotherapy, as well as the potential applications of metronomic chemotherapy and immune checkpoint inhibitors in the treatment of locoregionally advanced NPC.


Assuntos
Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Biomarcadores Tumorais , Quimiorradioterapia , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas
16.
J Hematol Oncol ; 13(1): 22, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188475

RESUMO

Methylation of RNA and DNA, notably in the forms of N6-methyladenosine (m6A) and 5-methylcytosine (5mC) respectively, plays crucial roles in diverse biological processes. Currently, there is a lack of knowledge regarding the cross-talk between m6A and 5mC regulators. Thus, we systematically performed a pan-cancer genomic analysis by depicting the molecular correlations between m6A and 5mC regulators across ~ 11,000 subjects representing 33 cancer types. For the first time, we identified cross-talk between m6A and 5mC methylation at the multiomic level. Then, we further established m6A/5mC epigenetic module eigengenes by combining hub m6A/5mC regulators and informed a comprehensive epigenetic state. The model reflected status of the tumor-immune-stromal microenvironment and was able to predict patient survival in the majority of cancer types. Our results lay a solid foundation for epigenetic regulation in human cancer and pave a new road for related therapeutic targets.


Assuntos
5-Metilcitosina/metabolismo , Adenosina/análogos & derivados , Epigênese Genética , Neoplasias/genética , 5-Metilcitosina/imunologia , Adenosina/genética , Adenosina/imunologia , Metilação de DNA , Redes Reguladoras de Genes , Genômica , Humanos , Neoplasias/diagnóstico , Neoplasias/imunologia , Prognóstico , Microambiente Tumoral
17.
Am J Chin Med ; 48(2): 329-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32138530

RESUMO

Dengue fever is an important epidemic disease with a high prevalence in tropical and subtropical countries. We aimed to investigate the effects of a treatment integrating traditional Chinese (TCM) and Western medicines on dengue inpatients with warning signs (i.e., group B) according to the World Health Organization dengue classification in this retrospective cohort study of medical records. Inpatients who were treated with conventional Western therapies in the absence or presence of TCM were assigned to the control and treatment groups, respectively. Data were compared using an analysis of variance, general linear analysis, and chi-square test. The most common clinical symptoms and signs of dengue fever were fever and muscle ache. The treatment group patients were significantly more likely to present general weakness and poor appetite than the control group patients. Patients in the treatment group were more likely to experience stomachache than those in the control group. Moreover, comparisons of the changes in hemoglobin and alanine aminotransferase levels over time revealed significant differences between the patient groups. Zhu Ye Shi Gao Tang, Gui Pi Tang, Paeonia suffruticosa, and Clerodendrum cyrtophyllum were the most commonly administered TCM formula and single herbs in this study. Patients in the treatment group experienced a resolution of symptoms, signs, and laboratory data and were discharged smoothly, without deterioration to death or critical care. Our findings suggest that the integration of TCM and Western medicine may yield an appropriate treatment for dengue fever.


Assuntos
Clerodendrum , Dengue/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Paeonia , Fitoterapia , Alanina Transaminase/metabolismo , Estudos de Coortes , Febre/tratamento farmacológico , Hemoglobinas/metabolismo , Humanos , Mialgia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
18.
Sci Rep ; 9(1): 15679, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666656

RESUMO

The diagnosis of periprosthetic joint infection (PJI) remains a challenge. However, recent studies showed that synovial fluid biomarkers have demonstrated greater diagnostic accuracy than the currently used PJI diagnostic tests. In many diagnostic tests, combining several biomarkers into panels is critical for improving diagnostic efficiency, enhancing the diagnostic precision for specific diseases, and reducing cost. In this study, we prove that combining alpha-defensin and C-reactive protein (CRP) as biomarkers possesses the potential to provide accurate PJI diagnosis. To further verify the result, we developed a multi-target lateral flow immunoassay strip (msLFIA) with staking pad design to obtain on-site rapid response for clinical diagnosis of PJI. A total of 10 synovial fluid samples were tested using the msLFIA, and the results showed that the combined measurements of synovial fluid alpha-defensin and CRP levels were consistent with those obtained from a commercial enzyme-linked immunosorbent assay kit. In addition, we developed a multi-target lateral flow immunoassay strip (msLFIA) with staking pad design to obtain on-site rapid response for clinical diagnosis of PJI, which the multi-target design is used to increase specificity and the stacking pad design is to enhance detection sensitivity. As a result, the turnaround time of the highly sensitive test can be limited from several hours to 20 min. We expect that the developed msLFIA possesses the potential for routine monitoring of PJI as a convenient, low-cost, rapid and easy to use detection device for PJI.


Assuntos
Artrite Infecciosa/diagnóstico , Proteína C-Reativa/isolamento & purificação , Infecções Relacionadas à Prótese/diagnóstico , alfa-Defensinas/isolamento & purificação , Artrite Infecciosa/metabolismo , Artrite Infecciosa/patologia , Artroplastia de Quadril/efeitos adversos , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Ouro/química , Humanos , Masculino , Nanopartículas Metálicas/química , Infecções Relacionadas à Prótese/metabolismo , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/patologia , Reoperação , Líquido Sinovial/metabolismo , Líquido Sinovial/microbiologia , alfa-Defensinas/metabolismo
19.
J Immunother Cancer ; 7(1): 298, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722750

RESUMO

BACKGROUND: Immunotherapy, especially immune checkpoint inhibition, has provided powerful tools against cancer. We aimed to detect the expression of common immune checkpoints and evaluate their prognostic values in nasopharyngeal carcinoma (NPC). METHODS: The expression of 9 immune checkpoints consistent with 13 features was detected in the training cohort (n = 208) by immunohistochemistry and quantified by computational pathology. Then, the LASSO cox regression model was used to construct an immune checkpoint-based signature (ICS), which was validated in a validation cohort containing 125 patients. RESULTS: High positive expression of PD-L1 and B7-H4 was observed in tumour cells (TCs), whereas PD-L1, B7-H3, B7-H4, IDO-1, VISTA, ICOS and OX40 were highly expressed in tumour-associated immune cells (TAICs). Eight of the 13 immune features were associated with patient overall survival, and an ICS classifier consisting of 5 features (B7-H3TAIC, IDO-1TAIC, VISTATAIC, ICOSTAIC, and LAG3TAIC) was established. Patients with high-risk scores in the training cohort had shorter overall (P < 0.001), disease-free (P = 0.002), and distant metastasis-free survival (P = 0.004), which were confirmed in the validation cohort. Multivariate analysis revealed that the ICS classifier was an independent prognostic factor. A combination of the ICS classifier and TNM stage had better prognostic value than the TNM stage alone. In addition, the ICS classifier was significantly associated with survivals in patients with high EBV-DNA load. CONCLUSIONS: We determined the expression status of nine immune checkpoints consistent with 13 features in NPC and further constructed an ICS prognostic model, which might add prognostic value to the TNM staging system.


Assuntos
Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Antígenos CD/imunologia , Antígenos B7/imunologia , Antígeno B7-H1/imunologia , Biologia Computacional , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Estimativa de Kaplan-Meier , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Prognóstico , Receptores OX40/imunologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/imunologia
20.
Ther Adv Med Oncol ; 11: 1758835919877729, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598143

RESUMO

Background: Few studies have evaluated the prognostic value of the integrated model consisting of gross tumor volume of lymph nodes (GTVnd) and pretreatment plasma Epstein-Barr virus DNA (pre-EBV DNA) in nasopharyngeal carcinoma (NPC) patients. Methods: A well-established big-data intelligence platform with 10,126 NPC patients was used for a retrospective review. A total of 1500 cases with cervical nodal metastases but without distant metastases were randomly assigned to a training (n = 503) or test condition (n = 997) for analyses. The cut-off point for the GTVnd derived from the receiver operating characteristic (ROC) curve was combined with the published cut-off point for pre-EBV DNA to develop an integrated model by which patients were classified into four groups. Results: Both GTVnd and pre-EBV DNA were independent prognostic factors. Regardless of whether patients received induction chemotherapy (IC), the 5-year distant metastasis-free survival (DMFS) (69.5%) and overall survival (OS) (68.4%) were significantly worse in those with both a GTVnd >20 ml and pre-EBV DNA >2000 copies/ml (all p-values < 0.001). In patients with IC, all others had better 5-year DMFS and OS; in patients without IC, those with either a GTVnd >20 ml or pre-EBV DNA >2000 copies/ml had the medium 5-year DMFS and OS, while patients with neither of them had the best. Conclusions: The integrated GTVnd and pre-EBV DNA model not only predicted DMFS and OS in NPC patients effectively, but was an indicator of timely adjustment of therapeutic strategies for NPC patients, especially those completing IC.

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